Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical region at chromosome 2q33-q34: Candidate genes for ALS2

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease th at manifests as selective upper and lower motor neuron degeneration. The au tosomal recessive form of juvenile amyotrophic lateral sclerosis (ALS2) has previously been mapped to the 1.7-cM interval flanked by D2S116 and D2S223 7 on human chromosome 2q33-q34. We identified three novel full-length trans cripts encoded by three distinct genes (HGMW-approved symbols ALS2CR1, ALS2 CR2, and ALS2CR3) within the ALS2 critical region. The intron-exon organiza tions of these genes as well as those of CFLAR, CASP10, and CASP8, which we re previously mapped to this region, mere defined. These genes were evaluat ed for mutations in ALS2 patients, and no disease-associated sequence alter ations in either exons or intron-exon boundaries were observed. Sequence an alysis of overlapping RT-PCR products covering the whole coding sequence fo r each transcript revealed no aberrant mRNA sequences. These data strongly indicate that ALS2CR1, ALS2CK2, ALS2CR3, CFLAR, CASP10, and CASP8 are not c ausative genes for ALS2. (C) 2001 Academic Press.